Abstract LB-347: A microRNA signature harbors prognostic implications in clear cell renal carcinoma (ccRC)

Abstract

Abstract Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies in the United States, and represents the most common cancer in the adult kidney. The most frequent histotype of RCC is the clear-cell variant (ccRCC) which occurs in 80–90% of RCC cases. Despite the advent of new target-oriented therapies, a radical surgery still represents the best option for patients diagnosed with ccRC, and the prognosis remains severe in case of disseminated disease. Unfortunately, post-nephrectomy recurrence rates for those patients with locally aggressive tumors are still high (35–65%), providing the rationale for an adjuvant treatment. Actually there is currently no established adjuvant therapy for RCC, although there are several ongoing clinical trials trying to address the question on whether an adjuvant treatment is effective after radical surgery for RCC, and what would the best treatment be. Undoubtedly, a better stratification of which patients are at highest risk of recurrence after radical nephrectomy would be of great benefit to establish which patients will benefit more of an adjuvant treatment, and/or of a closer follow-up. MicroRNAs (miRNAs) are short, non-coding RNAs with gene regulatory functions, whose expression has been shown to be de-regulated in almost all human tumors, including ccRCC. In some cases, specific signatures of de-regulated miRNAs harbor prognostic implications. In order to determine whether miRNAs are de-regulated in ccRC and a prognostic signature of de-regulated miRNAs can be identified, we collected 136 frozen paired normal and tumoral tissues from stage I ccRC patients. Then, we determined the expression of 476 different miRNAs between tumors and the normal renal tissue counterpart from the same patient, by using version 4.0 of the non-coding microarray developed at the Ohio State University. We confirmed, as described also by other Authors, that miRNAs are differentially expressed in tumor tissues versus the normal kidney counterpart, and we validated this diagnostic signature by quantitative real-time PCR (qRT-PCR). We then correlated the expression of miRNAs in the primary tumor samples, with the overall survival (OS) of our patients (calculated from the date of response to the date of the last follow-up or death, whichever occurred first), and for each miRNA, OS was estimated by Kaplan-Meier analysis. We observed that the expression of 10 miRNAs (namely, miR-23a*, miR-204, miR-211, miR-337–3p, miR-453, miR-566, miR-570, miR-574–3p, miR-599, and miR-603) was significantly altered in stage I ccRC patients with shorter OS, with respect to patients with better OS. Overall, this study identifies a prognostic signature of miRNAs, correlating with survival in stage I ccRC patients, and could lead to the identification of a new molecular parameter for a better stratification of ccRC patients necessitating adjuvant treatments and/or a closer post-surgery clinical follow-up. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-347. doi:10.1158/1538-7445.AM2011-LB-347